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Title: Early osteoinductive human bone marrow mesenchymal stromal/stem cells support an enhanced hematopoietic cell expansion with altered chemotaxis- and adhesion-related gene expression profiles

Abstract

Bone marrow (BM) microenvironment has a crucial role in supporting hematopoiesis. Here, by using a microarray analysis, we demonstrate that human BM mesenchymal stromal/stem cells (MSCs) in an early osteoinductive stage (e-MSCs) are characterized by unique hematopoiesis-associated gene expression with an enhanced hematopoiesis-supportive ability. In comparison to BM-MSCs without osteoinductive treatment, gene expression in e-MSCs was significantly altered in terms of their cell adhesion- and chemotaxis-related profiles, as identified with Gene Ontology and Gene Set Enrichment Analysis. Noteworthy, expression of the hematopoiesis-associated molecules CXCL12 and vascular cell adhesion molecule 1 was remarkably decreased in e-MSCs. e-MSCs supported an enhanced expansion of CD34{sup +} hematopoietic stem and progenitor cells, and generation of myeloid lineage cells in vitro. In addition, short-term osteoinductive treatment favored in vivo hematopoietic recovery in lethally irradiated mice that underwent BM transplantation. e-MSCs exhibited the absence of decreased stemness-associated gene expression, increased osteogenesis-associated gene expression, and apparent mineralization, thus maintaining the ability to differentiate into adipogenic cells. Our findings demonstrate the unique biological characteristics of e-MSCs as hematopoiesis-regulatory stromal cells at differentiation stage between MSCs and osteoprogenitor cells and have significant implications in developing new strategy for using pharmacological osteoinductive treatment to support hematopoiesis in hematopoietic stem and progenitor cellmore » transplantation. - Highlights: • Human BM-MSCs in an early osteoinductive stage (e-MSCs) support hematopoiesis. • Adhesion- and chemotaxis-associated gene signatures are altered in e-MSCs. • Expression of CXCL12 and VCAM1 is remarkably decreased in e-MSCs. • e-MSCs are at differentiation stage between MSCs and osteoprogenitor cells. • Osteoinductive treatment favors hematopoietic recovery after BMT in mice.« less

Authors:
 [1];  [2];  [3];  [3]; ;  [3];  [2];  [1];  [2];  [3];  [1];  [4];  [3]
  1. Department of Hematology/Oncology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507 (Japan)
  2. (Japan)
  3. Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507 (Japan)
  4. Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553 (Japan)
Publication Date:
OSTI Identifier:
22594187
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 469; Journal Issue: 4; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIGENS; BLOOD FORMATION; BONE MARROW; CONNECTIVE TISSUE CELLS; HEMOGLOBIN; IN VITRO; IN VIVO; IRRADIATION; LEUKOCYTES; LIGANDS; LYMPHOKINES; MICE; MINERALIZATION; MOLECULES; POLYMERASE CHAIN REACTION; SKELETON; STEM CELLS; STIMULATION; TRANSCRIPTION

Citation Formats

Sugino, Noriko, Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507, Miura, Yasuo, E-mail: ym58f5@kuhp.kyoto-u.ac.jp, Yao, Hisayuki, Iwasa, Masaki, Fujishiro, Aya, Division of Gastroenterology and Hematology, Shiga University of Medical Science, Shiga 520-2192, Fujii, Sumie, Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507, Hirai, Hideyo, Takaori-Kondo, Akifumi, Ichinohe, Tatsuo, and Maekawa, Taira. Early osteoinductive human bone marrow mesenchymal stromal/stem cells support an enhanced hematopoietic cell expansion with altered chemotaxis- and adhesion-related gene expression profiles. United States: N. p., 2016. Web. doi:10.1016/J.BBRC.2015.12.061.
Sugino, Noriko, Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507, Miura, Yasuo, E-mail: ym58f5@kuhp.kyoto-u.ac.jp, Yao, Hisayuki, Iwasa, Masaki, Fujishiro, Aya, Division of Gastroenterology and Hematology, Shiga University of Medical Science, Shiga 520-2192, Fujii, Sumie, Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507, Hirai, Hideyo, Takaori-Kondo, Akifumi, Ichinohe, Tatsuo, & Maekawa, Taira. Early osteoinductive human bone marrow mesenchymal stromal/stem cells support an enhanced hematopoietic cell expansion with altered chemotaxis- and adhesion-related gene expression profiles. United States. doi:10.1016/J.BBRC.2015.12.061.
Sugino, Noriko, Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507, Miura, Yasuo, E-mail: ym58f5@kuhp.kyoto-u.ac.jp, Yao, Hisayuki, Iwasa, Masaki, Fujishiro, Aya, Division of Gastroenterology and Hematology, Shiga University of Medical Science, Shiga 520-2192, Fujii, Sumie, Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507, Hirai, Hideyo, Takaori-Kondo, Akifumi, Ichinohe, Tatsuo, and Maekawa, Taira. Fri . "Early osteoinductive human bone marrow mesenchymal stromal/stem cells support an enhanced hematopoietic cell expansion with altered chemotaxis- and adhesion-related gene expression profiles". United States. doi:10.1016/J.BBRC.2015.12.061.
@article{osti_22594187,
title = {Early osteoinductive human bone marrow mesenchymal stromal/stem cells support an enhanced hematopoietic cell expansion with altered chemotaxis- and adhesion-related gene expression profiles},
author = {Sugino, Noriko and Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507 and Miura, Yasuo, E-mail: ym58f5@kuhp.kyoto-u.ac.jp and Yao, Hisayuki and Iwasa, Masaki and Fujishiro, Aya and Division of Gastroenterology and Hematology, Shiga University of Medical Science, Shiga 520-2192 and Fujii, Sumie and Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507 and Hirai, Hideyo and Takaori-Kondo, Akifumi and Ichinohe, Tatsuo and Maekawa, Taira},
abstractNote = {Bone marrow (BM) microenvironment has a crucial role in supporting hematopoiesis. Here, by using a microarray analysis, we demonstrate that human BM mesenchymal stromal/stem cells (MSCs) in an early osteoinductive stage (e-MSCs) are characterized by unique hematopoiesis-associated gene expression with an enhanced hematopoiesis-supportive ability. In comparison to BM-MSCs without osteoinductive treatment, gene expression in e-MSCs was significantly altered in terms of their cell adhesion- and chemotaxis-related profiles, as identified with Gene Ontology and Gene Set Enrichment Analysis. Noteworthy, expression of the hematopoiesis-associated molecules CXCL12 and vascular cell adhesion molecule 1 was remarkably decreased in e-MSCs. e-MSCs supported an enhanced expansion of CD34{sup +} hematopoietic stem and progenitor cells, and generation of myeloid lineage cells in vitro. In addition, short-term osteoinductive treatment favored in vivo hematopoietic recovery in lethally irradiated mice that underwent BM transplantation. e-MSCs exhibited the absence of decreased stemness-associated gene expression, increased osteogenesis-associated gene expression, and apparent mineralization, thus maintaining the ability to differentiate into adipogenic cells. Our findings demonstrate the unique biological characteristics of e-MSCs as hematopoiesis-regulatory stromal cells at differentiation stage between MSCs and osteoprogenitor cells and have significant implications in developing new strategy for using pharmacological osteoinductive treatment to support hematopoiesis in hematopoietic stem and progenitor cell transplantation. - Highlights: • Human BM-MSCs in an early osteoinductive stage (e-MSCs) support hematopoiesis. • Adhesion- and chemotaxis-associated gene signatures are altered in e-MSCs. • Expression of CXCL12 and VCAM1 is remarkably decreased in e-MSCs. • e-MSCs are at differentiation stage between MSCs and osteoprogenitor cells. • Osteoinductive treatment favors hematopoietic recovery after BMT in mice.},
doi = {10.1016/J.BBRC.2015.12.061},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 4,
volume = 469,
place = {United States},
year = {2016},
month = {1}
}